Glutathione S-Transferase Genotype Protects against In Utero Tobacco-linked Lung Function Deficits

Louisa Owens, Ingrid A. Laing, Jasminka Murdzoska, Guicheng Zhang, Steve W. Turner, Peter N. Le Souef

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rationale: In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.

Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.

Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).

Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, P = 0.021; -3.35% predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2% predicted, P = 0.01; -4.7% predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.

Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.

Original languageEnglish
Pages (from-to)462-470
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume200
Issue number4
DOIs
Publication statusPublished - 15 Aug 2019

Cite this

@article{fa9fc5b5a69d4f1f99be21b0c2636782,
title = "Glutathione S-Transferase Genotype Protects against In Utero Tobacco-linked Lung Function Deficits",
abstract = "Rationale: In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87{\%} predicted, P = 0.021; -3.35{\%} predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2{\%} predicted, P = 0.01; -4.7{\%} predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.",
keywords = "respiratory function tests, population genetics, detoxification, gene-environment interaction, tobacco smoke pollution, SMOKE EXPOSURE, MATERNAL SMOKING, CHILDHOOD, ASTHMA, POLYMORPHISMS, STANDARDIZATION, LOCUS, MU",
author = "Louisa Owens and Laing, {Ingrid A.} and Jasminka Murdzoska and Guicheng Zhang and Turner, {Steve W.} and {Le Souef}, {Peter N.}",
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Glutathione S-Transferase Genotype Protects against In Utero Tobacco-linked Lung Function Deficits. / Owens, Louisa; Laing, Ingrid A.; Murdzoska, Jasminka; Zhang, Guicheng; Turner, Steve W.; Le Souef, Peter N.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 200, No. 4, 15.08.2019, p. 462-470.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glutathione S-Transferase Genotype Protects against In Utero Tobacco-linked Lung Function Deficits

AU - Owens, Louisa

AU - Laing, Ingrid A.

AU - Murdzoska, Jasminka

AU - Zhang, Guicheng

AU - Turner, Steve W.

AU - Le Souef, Peter N.

PY - 2019/8/15

Y1 - 2019/8/15

N2 - Rationale: In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, P = 0.021; -3.35% predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2% predicted, P = 0.01; -4.7% predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.

AB - Rationale: In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, P = 0.021; -3.35% predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2% predicted, P = 0.01; -4.7% predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.

KW - respiratory function tests

KW - population genetics

KW - detoxification

KW - gene-environment interaction

KW - tobacco smoke pollution

KW - SMOKE EXPOSURE

KW - MATERNAL SMOKING

KW - CHILDHOOD

KW - ASTHMA

KW - POLYMORPHISMS

KW - STANDARDIZATION

KW - LOCUS

KW - MU

U2 - 10.1164/rccm.201807-1332OC

DO - 10.1164/rccm.201807-1332OC

M3 - Article

VL - 200

SP - 462

EP - 470

JO - American Journal of Respiratory Critical Care Medicine

JF - American Journal of Respiratory Critical Care Medicine

SN - 1073-449X

IS - 4

ER -